Search

Intestinal tuft cells are critical for anti-helminth parasite immunity because they produce IL-25, which triggers IL-13 secretion by activated group 2 innate lymphoid cells (ILC2s) to expand both goblet and tuft cells. We show that epithelial Elp3, a tRNA-modifying enzyme, promotes tuft cell differentiation and is consequently critical for IL-25 production, ILC2 activation, goblet cell expansion and control of Nippostrongylus brasiliensis helminth infection in mice. Elp3 is essential for the generation of intestinal immature tuft cells and for the IL-13-dependent induction of glycolytic enzymes such as Hexokinase 1 and Aldolase A. Importantly, loss of epithelial Elp3 in the intestine blocks the codon-dependent translation of the Gator1 subunit Nprl2, an mTORC1 inhibitor, which consequently enhances mTORC1 activation and stabilizes Atf4 in progenitor cells. Likewise, Atf4 overexpression in mouse intestinal epithelium blocks tuft cell differentiation in response to intestinal helminth infection. Collectively, our data define Atf4 as a negative regulator of tuft cells and provide insights into promotion of intestinal type 2 immune response to parasites through tRNA modifications., (© 2024. The Author(s).)

Background: The law regulating the forced or protective admission of the mentally ill person in Belgium is 34 years old. The parliament recently agreed on an extensive legislative amendment to better adapt the law to the changing mental health care system and society., Aim: Outlining the epidemiological, clinical and legal developments regarding forced admissions in Belgium., Method: Analysis of epidemiological data, evolutions in clinical practice and the previous and new legislative framework., Results: The incidence of forced admission in Flanders rised, with large provincial differences. Care for involuntarily admitted patients has evolved significantly in recent years, including the establishment of High and Intensive Care Units. The amended law allows a more thorough clinical evaluation before forced admission. More diversification and customization of protective measures become possible., Conclusion: The new law addresses a number of problems with the previous legislative framework. A number of points for improvement remain, which will hopefully be picked up by policy makers in further initiatives.

The cerebral cortex is the brain's outermost layer. It is responsible for processing motor and sensory information that support high-level cognitive abilities and shape personality. Its development and functional organization strongly rely on cell communication that is established via an intricate system of diffusible signals and physical contacts during development. Interfering with this cellular crosstalk can cause neurodevelopmental disorders. Here, we review how crosstalk between migrating cells and their environment influences cerebral cortex development, ranging from neurogenesis to synaptogenesis and assembly of cortical circuits., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Macrophage polarization is a process whereby macrophages acquire distinct effector states (M1 or M2) to carry out multiple and sometimes opposite functions. We show here that translational reprogramming occurs during macrophage polarization and that this relies on the Elongator complex subunit Elp3, an enzyme that modifies the wobble uridine base U34 in cytosolic tRNAs. Elp3 expression is downregulated by classical M1-activating signals in myeloid cells, where it limits the production of pro-inflammatory cytokines via FoxO1 phosphorylation, and attenuates experimental colitis in mice. In contrast, alternative M2-activating signals upregulate Elp3 expression through a PI3K- and STAT6-dependent signaling pathway. The metabolic reprogramming linked to M2 macrophage polarization relies on Elp3 and the translation of multiple candidates, including the mitochondrial ribosome large subunit proteins Mrpl3, Mrpl13, and Mrpl47. By promoting translation of its activator Ric8b in a codon-dependent manner, Elp3 also regulates mTORC2 activation. Elp3 expression in myeloid cells further promotes Wnt-driven tumor initiation in the intestine by maintaining a pool of tumor-associated macrophages exhibiting M2 features. Collectively, our data establish a functional link between tRNA modifications, mTORC2 activation, and macrophage polarization., (© 2022 The Authors. Published under the terms of the CC BY 4.0 license.)

Background: Antipsychotics are considered the cornerstone for the treatment of schizophrenia and are increasingly used in the treatment of mood disorders. A lack of drug adherence is a frequently occurring problem. Depot antipsychotics have been co-developed in order to deal with this problem., Aim: To map the depot antipsychotics prescription behaviour of psychiatrists and general practitioners in outpatient practice in Belgium., Method: Analysis of sales data of antipsychotics between 1997 and 2016. Data were supplied by Pharmanet, a database within the National Institute for Health and Disability Insurance (NIHDI)., Results: In the period 1997-2004, outpatient sales of depot antipsychotics decreased by 20%. The portion of depot antipsychotics in total antipsychotics sales dropped from 14.9% (1997) to 8.5% (2004). After second-generation depot antipsychotics were introduced from 2004, the sales figures of depot antipsychotics increased by 83%. In 2016, 9.8% of antipsychotic prescriptions was a depot antipsychotic prescription. As of 2012, more second-generation depot antipsychotics (52.2%) were sold than first-generation depot antipsychotics (47.8%). Psychiatrists were quicker to adopt second-generation depot antipsychotics than general practitioners, a trend similar to oral antipsychotics., Conclusion: Outpatient sales of depot antipsychotics in Belgium were on the rise after second-generation long-acting preparations were introduced to the market. Recent Scandinavian studies suggest that an increase in prescription of depot antipsychotics may contribute to better clinical outcomes.

We describe here a protocol to assess NF-κB activation in ex-vivo organoids generated from mouse intestinal crypts. These structures are maintained in culture as crypt-villus forming organoids. These ex-vivo organoids maintain both self-renewal and multilineage differentiation overtime. We also describe the generation of ex-vivo organoids from Apc-mutated mouse intestinal crypts. Both wild-type and Apc-mutated organoids respond very well to NF-κB-activating signals such as TNFα but not to LPS. The kinetic of NF-κB activation in response to these signals in ex-vivo intestinal organoids is very similar to what we see in 2D cell lines. This protocol provides investigators a powerful tool to assess NF-κB activation in both healthy and transformed intestinal epitheliums maintained in culture as 3D structures.

Transcranial Magnetic Stimulation (TMS) is a form of non-invasive brain stimulation, used to alter cortical excitability both in research and clinical applications. The intermittent and continuous Theta Burst Stimulation (iTBS and cTBS) protocols have been shown to induce opposite after-effects on human cortex excitability. Animal studies have implicated synaptic plasticity mechanisms long-term potentiation (LTP, for iTBS) and depression (LTD, for cTBS). However, the neural basis of TMS effects has not yet been studied in human neuronal cells, in particular at the level of gene expression and synaptogenesis. To investigate responses to TBS in living human neurons, we differentiated human SH-SY5Y cells toward a mature neural phenotype, and stimulated them with iTBS, cTBS, or sham (placebo) TBS. Changes in (a) mRNA expression of a set of target genes (previously associated with synaptic plasticity), and (b) morphological parameters of neurite outgrowth following TBS were quantified. We found no general effects of stimulation condition or time on gene expression, though we did observe a significantly enhanced expression of plasticity genes NTRK2 and MAPK9 24 h after iTBS as compared to sham TBS. This specific effect provides unique support for the widely assumed plasticity mechanisms underlying iTBS effects on human cortex excitability. In addition to this protocol-specific increase in plasticity gene expression 24 h after iTBS stimulation, we establish the feasibility of stimulating living human neuron with TBS, and the importance of moving to more complex human in vitro models to understand the underlying plasticity mechanisms of TBS stimulation., (Copyright © 2020 Thomson, Kenis, Tielens, de Graaf, Schuhmann, Rutten and Sack.)

Knowledge of the geographical distribution of soils is indispensable for policy and decision makers to achieve the goal of increasing agricultural production and reduce poverty, particularly in the Global South. A study was conducted to better understand the soilscapes of the Giba catchment (900-3300 m a.s.l.; 5133 km2) in northern Ethiopia, so as to sustain soil use and management. To characterise the chemical and physical properties of the different benchmark soils and to classify them in line with the World Reference Base of Soil Resources, 141 soil profile pits and 1381 soil augerings at representative sites were analysed. The dominant soil units identified are Leptosol and bare rock (19% coverage), Vertic Cambisol (14%), Regosol and Cambisol (10%), Skeletic/Leptic Cambisol and Regosol (9%), Rendzic Leptosol (7%), Calcaric/Calcic Vertisol (6%), Chromic Luvisol (6%) and Chromic/Pellic Vertisol (5%). Together these eight soil units cover almost 75% of the catchment. Topography and parent material are the major influencing factors that explain the soil distribution. Besides these two factors, land cover that is strongly impacted by human activities, may not be overlooked. Our soil suitability study shows that currently, after thousands of years of agricultural land use, a new dynamic equilibrium has come into existence in the soilscape, in which ca. 40% of the catchment is very suitable, and 25% is moderately suitable for agricultural production. In view of such large suitable areas, the Giba catchment has a good agricultural potential if soil erosion rates can be controlled, soil fertility (particularly nitrogen) increased, available water optimally used, and henceforth crop yields increased., Competing Interests: The authors have declared that no competing interests exist.

Interneurons navigate along multiple tangential paths to settle into appropriate cortical layers. They undergo a saltatory migration paced by intermittent nuclear jumps whose regulation relies on interplay between extracellular cues and genetic-encoded information. It remains unclear how cycles of pause and movement are coordinated at the molecular level. Post-translational modification of proteins contributes to cell migration regulation. The present study uncovers that carboxypeptidase 1, which promotes post-translational protein deglutamylation, controls the pausing of migrating cortical interneurons. Moreover, we demonstrate that pausing during migration attenuates movement simultaneity at the population level, thereby controlling the flow of interneurons invading the cortex. Interfering with the regulation of pausing not only affects the size of the cortical interneuron cohort but also impairs the generation of age-matched projection neurons of the upper layers., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

The migration of cortical interneurons is a fundamental process for the establishment of cortical connectivity and its impairment underlies several neurological disorders. During development, these neurons are born in the ganglionic eminences and they migrate tangentially to populate the cortical layers. This process relies on various morphological changes that are driven by dynamic cytoskeleton remodelings. By coupling time lapse imaging with molecular analyses, we show that the Elongator complex controls cortical interneuron migration in mouse embryos by regulating nucleokinesis and branching dynamics. At the molecular level, Elongator fine-tunes actomyosin forces by regulating the distribution and turnover of actin microfilaments during cell migration. Thus, we demonstrate that Elongator cell-autonomously promotes cortical interneuron migration by controlling actin cytoskeletal dynamics.

The cerebral cortex is one of the most intricate regions of the brain that requires elaborate cell migration patterns for its development. Experimental observations show that projection neurons migrate radially within the cortical wall, whereas interneurons migrate along multiple tangential paths to reach the developing cortex. Tight regulation of the cell migration processes ensures proper positioning and functional integration of neurons to specific cerebral cortical circuits. Disruption of neuronal migration often leads to cortical dysfunction and/or malformation associated with neurological disorders. Unveiling the molecular control of neuron migration is thus fundamental to understanding the physiological or pathological development of the cerebral cortex. In this unit, protocols allowing detailed analysis of patterns of migration of both interneurons and projection neurons under different experimental conditions (i.e., loss or gain of function) are presented., (Copyright © 2016 John Wiley & Sons, Inc.)